AB0707 Changes of immunoglobulin G and frequency of infections in systemic sclerosis patients during long-term rituximab therapy
Authors: L. Garzanova, L. P. Ananyeva, O. Koneva, O. Ovsyannikova, O. Desinova, M. Starovoytova, R. Shayakhmetova, A. Khelkovskaia-Sergeeva
Journal: Annals of the Rheumatic Diseases (2022)

Background Decrease of immunoglobulin G (IgG) could often be observed during rutuximab (RTX) therapy in systemic sclerosis (SSc) and other autoimmune diseases. Lower lever of IgG could be associated with an increased risk of secondary infectious complications. However, there are very few data on changes of IgG in SSc during long-term RTX therapy. Objectives To evaluate changes of Ig G and the frequency of infectious adverse events (AE) in SSc patients (pts) on RTX therapy during long-term follow-up. Methods Our prospective study included 78 pts with SSc received RTX therapy. The mean follow-up period was 50.2±23 months. The mean age was 48.2±13.7 years, female-64 pts (82%), the diffuse cutaneous subset of the disease had 48 pts (62%), limited - 24 (31%), overlap - 6 (7%). The mean disease duration was 5.4±3.4 years. 92% of pts were positive for ANA and 71% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.8±4.1 mg/day, immunosupressants at inclusion received 40% of them. The IgG was evaluated over the periods: at baseline (point 0), 12-18 mo (point 1), 24-60 mo (point 2) and 66-84 mo (point 3) after initiation of RTX therapy. IgG levels was measured using ELISA. Normal IgG reference values ranged within 7.0-16.0 g/l. AE were assessed and recorded by a physician at a hospital immediately after the infusion of RTX, then by patient reported outcome during the observation period. Severe AE were defined as those that required hospitalization for more than 24 hours and life-threatening situations. The results are presented in the form of mean values and standard deviations. Results There was a significant decrease of IgG during RTX therapy (Table 1). However, the level of IgG remained within normal limits. Initially lower level of IgG had 6 pts (8%). And further at point 1 there was 12 pts (15%) with decrease of IgG below normal limits, at point 2 - 12 pts (15%) and at point 3 - 5 pts (6%). When we compared the level of IgG between point 2 and 3 - no significant differences were found. Table 1. Changes of IgG level during RTX treatment. Parameters Point 0 (n=78) Point 1(n=78) Point 2(n=76) Point 3(n=27) PPoint 0-1 PPoint 0-2 PPoint 0-3 IgG, g/l, M±σ 12.3±4.2 10.6±3.4 9.6±2.8 9.6±2.6 0.0001 0.0001 0.01 Cumulative mean dose of RTX, g, M±σ - 1.8±0.5 3.9±1.3 4.8±2.1 - - - AE was evaluated over the period of 335.4 patient-years (PY). Infectious AE were reported in 34 patients (44%), the overall frequency was 10.2/100 PY (95% Confidence Interval (CI) 7.1-13.8). No serious opportunistic infections were reported. The highest frequency of infectious AE was observed in the first 2-6 months after the first infusion of RTX, however these were mainly mild AE (82%). The frequency of serious infections was 1.8/100 PY (95% CI 0.7-3.8). There was a decrease of infectious AE in the follow-up period (4.4/100 PY, 95% CI 2.5-7.2 – at period from 24 month of RTX therapy). Conclusion In our study, a significant decrease of IgG was noted in SSc pts during the first 5 years of RTX therapy, but later its level stabilized and remained within normal limits. A decrease of IgG in the first year after the initiation of RTX therapy was accompanied by an increase in the frequency of infectious AE. However, with an increase of the cumulative dose of RTX, there was no increase in infectious AE. Monitoring of IgG levels may be useful for SSc pts on RTX therapy for early identification of the risk for developing infectious complications. Disclosure of Interests None declared